Pregnancy-associated Protein Linked to Gestational Diabetes

by Colleen Fleiss on Dec 2 2020 5:03 AM

Pregnancy-associated Protein Linked to Gestational Diabetes
Low levels of pregnancy-associated plasma protein-A, known as PAPPA, commonly screened during the first trimester of pregnancy are linked to adipose tissue remodeling, glucose resistance, and gestational diabetes mellitus in pregnant women, stated //data by Silvia Corvera, MD, and Tiffany Moore Simas, MD, MPH, MEd, and colleagues.
The findings of the study are published in Science Translational Medicine.

"We currently evaluate women for gestational diabetes at 24 to 28 weeks of pregnancy, so there's only a short window of time when we can intervene clinically," said Dr. Moore Simas, chair and professor of obstetrics & gynecology.

Dr. Corvera, the Endowed Chair in Diabetes Research and professor of molecular medicine, added, "Gestational diabetes is a huge health problem not just for mothers, but also for children, because we know these metabolic changes can be passed on to the next generation. Children born from mothers with gestational diabetes are at higher risk for metabolic diseases and type 2 diabetes as they get older."

Gestational diabetes mellitus is one of the most common pregnancy complications, impacting as many as 5 to 9 percent of all pregnancies in the U.S.

In pregnant women, healthy expansion and accumulation of adipose tissue is a normal physiological change necessary to maintain proper nutrient levels for both mother and fetus.

Healthy adipose tissue is also essential for metabolism and glucose homeostasis. It keeps fat away from other organs, such as the heart and liver, where it can accumulate and cause disease.

Moore Simas, a practicing OB/GYN, often saw these physiological changes firsthand. "One of the things you notice when performing a C-section is that the appearance of the adipose tissues varies greatly from person to person," said Moore Simas. "These are observable differences in the internal adipose tissue around organs that didn't seem to necessarily correspond to the mother's weight."

To identify the factors contributing to differences between healthy and unhealthy adipose tissue in pregnant women, Corvera ran a series of RNA screens on adipose tissue from pregnant women after cesarean delivery so that they could identify possible differences in gene expression.

Findings identified the elevated presence of Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) in fat from pregnant women. IGFBP5 traps another Insulin-like Growth Factor-1 (IGF-1) protein necessary for cell proliferation and tissue growth.

Corvera and Moore Simas thought that the high levels of IGFBP5 in adipose tissue might be connected to a well-known protein, PAPPA. This protein, made by the placenta, continues to rise until the end of pregnancy and disappears once the placenta has been delivered.

Low levels of PAPPA have been used to screen for Down syndrome and other chromosomal disorders.

Researchers reviewed the medical records of 6,361 pregnant women to analyze PAPPA levels in the first trimester and compare them with blood glucose levels later in pregnancy. She found that lower PAPPA levels were correlated to increased insulin resistance and gestational diabetes later in pregnancy.

Researchers would also like to see if PAPPA levels can predict blood glucose levels, insulin resistance, and gestational diabetes before the presentation of clinical symptoms.

Corvera said, "Although very large amounts of PAPPA are made by the placenta during human pregnancy, it is possible that it may play a role outside pregnancy, as small amounts of PAPPA are also made in other tissues. In this way the PAPPA protein and the IGF-1 signaling pathway could play a role in the healthy development of adipose tissue outside of pregnancy and be relevant for other metabolic diseases. This is something we're eager to explore."


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